HIV-infected individuals face a markedly increased risk of cardiovascular disease (CVD), even when viremia is suppressed by combined antiretroviral therapy (cART). Mechanisms underlying HIV-associated CVD risk are incompletely understood and specific guidelines on cardioprotective care for this population are not available. Characterizing and reducing CVD risk among HIV-infected women represents a particular challenge. HIV-infected women have a lower prevalence of select traditional CVD risk factors (e.g., hypertension, smoking) and are less likely than HIV-infected men to be offered preventive cardiac care in clinical practice. However, several studies suggest women with HIV are just as likely as their male counterparts to incur an MI. Indeed, a large-scale US epidemiologic study shows that among HIV-infected women, unadjusted rates of MI modestly exceed those among HIV-infected men. Moreover, the same study reveals a significantly higher adjusted relative risk of MI in HIV infected-women versus uninfected females (2.89) as compared with HIV-infected men versus uninfected males (1.4). The proposed study aims to identify sex-specific mechanisms of CVD risk and risk reduction in HIV, addressing an NIH research priority. Importantly, the proposed study leverages the infrastructure of the largest primary prevention trial in the field of HIV-associated CVD: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE, A5332). The REPRIEVE trial, now launching, will test among 6500 HIV-infected persons ages 40-75 with low traditional CVD risk scores whether statin therapy reduces clinical cardiovascular events. Statin therapy has appeal in HIV in that it both reduces LDL cholesterol levels and dampens atherogenic immune activation, which persists in persons with HIV on cART. Work from our group and others suggests immune activation is highest in HIV-infected women (vs. HIV-infected men), particularly among those women who have undergone menopause. Through the proposed project, we will assess whether immune activation contributes uniquely to CVD risk among HIV-infected women across the reproductive aging spectrum and how statins may reduce CVD risk through effects on this pathway. Answers to these questions will influence the development of CVD prediction and prevention strategies tailored to the aging female HIV-infected population worldwide (~17 million). Maximizing our power to elucidate sex-specific CVD mechanisms in HIV, we will also design, implement, and evaluate the effectiveness of an evidence-based education/awareness recruitment campaign to enhance female enrollment in the REPRIEVE trial.